1. Technical Field of the Invention
Aspects of the present invention relate to prosthesis for people that suffer from peripheral vestibular disorders. In particular, aspects of the invention relate to a vestibular prosthesis that uses a neuromimetic model of the vestibular function.
2. General Background of the Invention
The peripheral vestibular apparatus resides in the inner ear and is located in the interior of the temporal bone in the bony labyrinth at the base of the cranium. This apparatus is responsible for the transduction of movement during changes in the dynamics of the primary vestibular neurons; the central vestibular nuclei comprise a group of neurons from the brainstem that are responsible of receiving, integrating and distributing the information controlling a set of motor activities, such as the movement of the eyes and the head; postural reflexes, autonomic reflexes and the generation of a spatial framework of the subject's movement within his or her environment, resulting in an efficient posture control, gaze stabilization and the generation of a spatial navigation map for the subject.
FIG. 1 schematizes the human vestibular system, which is constituted by a peripheral part (sensory receptors and afferent and efferent nerve pathways) and a central part (vestibular nuclei and their secondary connections with the brain cortex and other cephalic regions). The Utricle (U), Saccule (S) and the Superior (AC), Lateral (LC) and Posterior (PC) Semicircular Canals can be identified in the peripheral part. At a central level, the vestibular nerves project to the lateral (LVN), descending (DV), medial (MVN) and superior (SVN) vestibular nuclei. The vestibular sensory receptors are constituted by three semicircular canals located in three planes (horizontal and two anterior-posterior vertical planes) and by two otolithic membranes: the utricle and the saccule. The semicircular canals are formed by a hemicanal and a widened section known as the ampulla (anterior ampulla, horizontal ampulla and posterior ampulla) that has a region of sensitive cells itself (hair cells) and in which the sensitive portion presents two elements: one element formed by a gelatinous mass called cupula and another element with epithelium called ampullary crest, presenting supporting and hair cells.
The otolithic organs (saccule and utricle) are formed by an epithelial sac in which the sensory cells accumulate in a region of the epithelium (macula) with supporting cells and hair cells. There is a gelatinous mass on the epithelium known as otolithic mass, formed by calcium carbonate crystals (otoconia), embedded in a gelatinous matrix and surrounded by the otolithic membrane.
Mechanical stimuli have a different influence on each vestibular sensor: angular acceleration produces an inertial movement of the endolymph, flexing the cupula of the semicircular canals, and with them, the cilia of the sensory cells. Linear acceleration produces a displacement of the otolithic mass, which flexes the cilia bundle of the sensory cells of the macula's epithelium. Finally, in both types of organs, the result is the same: the cilia of the sensory cells are flexed. The displacement of the cilia bundle increases the aperture probability of the transduction channels, thus modifying the transduction currents. FIG. 2 shows the cellular process from acceleration until the activation of the vestibular afferent nerve. These are the processes whose sequence constitutes the basis of the mathematical model for the processing of information given by the gyroscope and the accelerometer.
The transduction current causes the hair cells to vary the membrane potential, followed by changes in the membrane's ionic currents, synaptic activation and the subsequent modification of the probability of generating action potentials in the afferent neurons.
The information transmitted from the vestibular organs informs the nervous system about the changes in the direction of the angular (turns) and linear movement. Having this information at its disposal, the brain is capable of correcting any imbalance related to the vestibular processes by means of the modification of the skeletal musculature's contraction. The vestibular system helps to correct posture, in addition to intervening in the displacement of the eyes. It should be noted that, in terms of balance, the vestibular system is the most specific receptor of the balance function from the triad of sensory receptors (proprioceptive, visual and vestibular) because, even though the three contribute to that function, the other two sensory systems, the proprioceptive and the visual, have other functions. The role of the vestibular system can be summarized in three necessary functions to preserve balance:
A. Formation of the sensation of spatial orientation
B. Preservation of body balance; reflexes at rest and in movement.
C. Stabilization of the head and the position of the eyes.
The main function of the vestibular system is to provide information about the spatial orientation of the head. Due to the fact that the vestibular apparatus provides this information regarding the head, it cannot make posture adjustments on its own. The sensors on the neck and maybe on other postural muscles are important to indicate related changes between the head and body to the central nervous system. This information is integrated at a central level, where, added to the proprioceptive and visual information, it allows establishing schemes for the position and dynamics of the organism's displacements. This complex process depends, therefore, on the visual environment and the control of the position of the eyes on the one hand, and on the other, on the information derived from the somatosensory and vestibular systems.
The diminished balance capacity, often considered in senior adults, poses a serious health hazard due to a greater probability of falling down. Vestibular alterations cause blurry or double vision, balance difficulties and the spatial symptoms of disorientation, vertigo, postural imbalance, nausea, vomit, among others, which are often signs of a vestibular system dysfunction. Symptoms can be mild or very severe and long lasting, resulting in total disability with a subsequent high economic cost. Several proposals to improve the sensation of balance and postural control can be taken into account. The appropriate medication can reduce some of the symptoms. Non-invasive exercises have a relatively low risk and can also improve vestibular function. If balance control cannot be improved using these methods, a vestibular prosthesis is an alternative way of restoring the balance function. Said device can be applied as a temporary aid during the recovery of an inner ear surgery or as a permanent prosthesis for subjects with severe vestibular damage and in senior adults prone to falling down.
In fact, for the person in the process of falling, it is more important to be able to “land” safely than to prevent a future fall. In cats, monkeys and human beings, the “landing” response depends, at least in part, on the vestibular function. In an extreme situation, the fall takes place during a very short period of time, not exceeding one second. Therefore, a 10-20-millisecond delay in the output signal of the vestibular apparatus (because of deterioration due to old age or because of a vestibule-specific pathology) leads to an unavoidable (uncontrollable) fall. The second cause of the uncontrollable fall is the quantitative change in the output signal, such as the loss of information of the otolithic organ or the semicircular canal, for example.
Due to the high incidence of vestibular alterations and their disabling effects, some vestibular prosthesis and aids have been developed. These consist of at least two categories. In a first category, the vestibular prosthesis provides information to the nervous system directly through the electrical stimulation of the vestibular pathways related to spatial orientation. In a second category, the vestibular prosthesis provides information via sensory substitution through the other sensory systems (tactile, visual, auditory, etc.).
Regarding the devices of the first category, research is currently being carried out to develop fully implantable vestibular prostheses, designed with Micro-Electric-Mechanical-System (MEMS) technology, consisting of gyroscopes and accelerometers, as well as integrated circuits (CI). The operation of these devices is based on the capacity to detect the acceleration the head is subjected to and the possibility of injecting pulses to the vestibular part of the brain. The following sensitivity parameters, among others, are taken into account: (a) the rotational perception threshold and (b) the linear acceleration sensitivity threshold in human beings, as well as (c) the neuron discharge rate and its relationship with the head's movements and rotations.
The vestibular prostheses in the second category are non-invasive in nature, that is to say, they do not need implants and are based on methods that allow the subject to obtain information about the acceleration the head is subjected to by means of other sensory organs (a sound or an electric stimulus on the skin, for example). In this case, the subject's adaptive plastic capacity and learning capabilities play an essential role in the operation of the prosthetic system.
Vestibular prostheses to aid the treatment of balance disorders in human beings are currently being researched. For example, Rubinstein and Phillips of the University of Washington's Medical Centre announced in October 2011 that one patient would be the first receptor in the world of an implant whose objective is the treatment of vertigo related to Meniere's disease (Meniere's disease is an inner ear disorder affecting the person's balance and hearing. The balance problems associated to this disease are produced due to an alteration in the inner ear's fluids with an endolymph accumulation). Up to now, this disease had been treated with medication, diet changes, exercise, and in the most severe cases, surgery. However, surgery normally means having to give up the capacity to hear in the affected ear with the purpose of stopping vertigo. The device developed by Rubinstein and Phillips of the University of Washington's Medical Centre, which is still being tested, is based in the commercial technology for cochlear implants with an electrode arrangement and a processor with software designed for its specialized use.
The patient carries a processor behind the auricle of the affected ear and, when an attack begins, the patient activates the device so that it operates during the periods when the vertigo takes place only. Said device transmits electrical impulses through three electrodes inserted in the canals of the bony labyrinth of the inner ear. The intensity of the stimulus and the efficiency of the vertigo suppression must be modulated with amplitude and frequency adjustments. Each semicircular canal receives an electrode arrangement.
Another device being researched is the one developed by Andrei Shkeel and collaborators from Irvine University in California. They are working in the design of a unilateral vestibular prosthesis whose detection element is a MEMS one-axis gyroscope. Similar to the semicircular canals, the microgyroscope detects the head's angular movements and generates proportional voltages to those corresponding to angular acceleration. The output of these detectors is sent to a pulse-generating unit, where the angular movement is translated into voltage pulses. The monophasic voltage pulses become biphasic current pulses and are conditioned to stimulate the corresponding branch of the vestibular nerve. On the other hand, Gong and Merfeld from Harvard University's Harvard Clinical and Translational Science Centre are researching a neural prosthesis of the semicircular canal using electrical stimulation. The device measures the head's angular velocity with a microgyroscope. The velocity is filtered digitally to modulate the frequency of the electrical stimulation pulse. The pulse varies between 50 and 250 Hz through a value table relating angular velocity to pulse frequency in a sigmoidal manner. A power source uses these pulses to deliver a balanced charge in the form of current pulses to the nerves innervating the semicircular canals through platinum electrodes. All the components of the device are found inside a light container measuring 43 mm×331 mm×325 mm approximately, which can be assembled in the upper part of the head.
Another device is the one developed by Charley C. Della Santina and collaborators from John Hopkins University in the United States, international patent applications WO-2011/088130, WO-2012/018631, United States patent application US-2005-0267549, in which the operation of a vestibular prosthesis that codifies three-dimensional movement to electrical impulse stimuli with a modulated frequency, with which the ampullary nerves are stimulated, is to described. This device has been studied in experimental animals, in which the ampullary nerves are stimulated, thus provoking turning responses and compensatory responses accompanied by—vestibule-ocular reflexes.
The international patent application WO 2011/088130 A2 (SANTINA, COLEMAN, FRIDMAN and CHIANG), published on Jul. 31, 2011, describes; an implantable vestibular prosthesis in which the device has a sensor system, a data processor connected to the sensor system and a nerve stimulation system connected to the data processor in order to provide electrical stimulation to at least one branch of at least one vestibulocochlear nerve. The nerve stimulation system includes an electrode arrangement with a first group of electrodes structured to be surgically implanted through an electrical connection with an upper pathway or branch of the vestibular nerve; a second group of electrodes structured to be surgically implanted through an electrical connection with a horizontal pathway or branch of the vestibular nerve; a third group of electrodes structured to be surgically implanted through an electrical connection with a posterior pathway or branch of the vestibular nerve; and a common cross electrode structured to be surgically implanted within the common cross of the vestibular labyrinth.
WO 2012/018631 A2 (SANTINA, COLEMAN, ANDREOU, KALAYJIAN, FRIDMAN and CHIANG), published on Feb. 9, 2012, describes a multi-channel vestibular prosthesis comprising: a sensor system; a microcontroller configured to communicate with the sensor system to receive the signals registered by the sensors while in operation, said microcontroller being configured to provide control signals in response to the signals from the sensors (registered); an integrated neuro-electronic interface circuit configured to communicate with the microcontroller to receive said control signals; and one group or set of electrodes electrically connected to said integrated neuro-electronic interface circuit; in which said integrated neuro-electronic interface circuit comprises: a digital controller configured to communicate with the microcontroller; a set of digital-to-analogue to converters configured to communicate with the digital controller; and a set of analogue current control circuits, each one of which is built to communicate respectively with each other; in which each one of said group of analogue current control circuits can be connected electrically to a respective electrode from a group of electrodes to deliver an electrical stimulus to at least one vestibular nerve, either directly or under software control; and in which said digital controller is configured to control amplitude, frequencies, polarities and duration of the currents to be delivered to any combination of said group of electric conductors.
These developments are incipient, however. The state of the art does not include a vestibular prosthesis that reproduces the processing of the natural vestibular information to mechanical stimuli (because the matter object of aspects of the present invention is a vestibular prosthesis). Therefore, there is a need for a vestibular prosthesis that compensates the loss of a person's vestibular function and related functions in the state of the art.